2.8Therapy

•The treatment of ALL is risk-adapted, depending on the different individual biological factors of ALL (clinical manifestation, laboratory analysis of morphology, cytochemistry, immunology, molecular cytogenetics, etc.)

•Early cooperation between a pediatric oncologist and the referring physician has to be established

•The treatment of ALL is subdivided into remission induction, consolidation with CNS prophylaxis, and maintenance phase. During the maintenance phase delayed intensification-phase, interim maintenance-phase etc., are used sometimes,

•Parents and patients should have a clear understanding of each stage of therapy and the side effects

2.8.1Induction of Remission

•Remission means disappearance of all signs of leukemia on clinical examination and peripheral blood analysis: bone marrow analysis with less than 5% leukemic cells morphologically, and normal hematopoiesis established. Much more sensitive methods of detecting leukemia or MRD are increasingly being used to define remission status

•Elimination of leukemic cells by a combination of vincristine, prednisone, and additional cytotoxic agents such as daunorubicin, doxorubicin, and l-asparaginase

•In parallel to induction treatment, decrease in hemoglobin, white blood cells, and platelets

•Duration of induction treatment: 4–5 weeks

•Regression of organ enlargement can be observed within the first 2 weeks

•Rate of first remission in ALL: more than 90%

•For prophylaxis of CNS leukemic disease, intrathecal chemotherapy usually methotrexate but cytosine arabinoside often given on first treatment before, during, and after remission has to be performed. The addition of preventive cranial irradiation has been omitted from some clinical trials but is still being studied in other cooperative group trials

2.8.2Consolidation Treatment

•Without continuation of treatment beyond remission, leukemia will reappear within weeks or months

•When remission with normal hematopoiesis is achieved, further intensive chemotherapy is necessary to reach a complete eradication of leukemic cells

•Combinations of different cytotoxic drugs reduce the number of remaining leukemic cells and the development of resistance against particular chemotherapies

•Special laboratory analysis (molecular and/or cytogenetic methods, flow cytometry) may detect minimal residual disease (MRD)